HCID 60628064, compound → HCID 69219298, compound

HRID 1394276Notes

Reaction equation

HRID 1394276 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][C:8]([N:17]([CH3:19])[CH3:18])([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.C1([O:26][C:27](=O)[NH:28][CH2:29][CH2:30][C:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[NH:33][CH:32]=2)C=CC=CC=1>O1CCOCC1>[CH3:18][N:17]([CH3:19])[C:8]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:7][CH2:6][CH:5]([CH2:4][CH2:3][CH2:2][NH:1][C:27]([NH:28][CH2:29][CH2:30][C:31]2[C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[NH:33][CH:32]=2)=[O:26])[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 60628064HCID 60628064, compoundHCID 69217980HCID 69217980, compound

Product 1

HCID 69219298HCID 69219298, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The mixture of [4-(3-aminopropyl)-1-phenyl-cyclohexyl]-dimethylamine (380 mg, 1.46 mmole) was added to a solution of [2-(1H-indol-3-yl)ethyl]carbamic acid phenyl ester (409 mg, 1.46 mmole) in dioxane (10 ml). The batch was then refluxed for 12 h. Working up was performed by removing the dioxane by distillation and combining the residue with water (10 ml). The batch was adjusted to pH 11 with 5M NaOH and extracted with EE (3×20 ml). The combined EE extracts were washed with 1M NaOH (5 ml) and dried with Na2SO4. The solvent was removed by distillation under a vacuum. The residue was the diastereoisomeric mixture of 1-[3-(4-dimethylamino-4-phenyl-cyclohexyl)-propyl]-3-[2-(1H-indol-3-yl)-ethyl]-urea, which was separated and purified by flash chromatography on silica gel (70 g). Methanol/EE (3:1, 1500 ml; 1:1, 500 ml; and 1:2, 1000 ml) was used as eluent. The more nonpolar diastereoisomer of 1-[3-(4-dimethylamino-4-phenyl-cyclohexyl)-propyl]-3-[2-(1H-indol-3-yl)-ethyl]-urea (Example 35, 95 mg, m.p. 126° C., 15%) and the more polar diastereoisomer of 1-[3-(4-dimethylamino-4-phenyl-cyclohexyl)-propyl]-3-[2-(1H-indol-3-yl)-ethyl]-urea (Example 36, 116 mg, m.p. 57° C., 18%) were isolated in this manner.

Workup

  1. temperatureThe batch was then refluxed for 12 h
  2. customby removing the dioxane
  3. distillationby distillation
  4. extractionextracted with EE (3×20 ml)
  5. washThe combined EE extracts were washed with 1M NaOH (5 ml)
  6. dry with materialdried with Na2SO4
  7. customThe solvent was removed by distillation under a vacuum
  8. additionthe diastereoisomeric mixture of 1-[3-(4-dimethylamino-4-phenyl-cyclohexyl)-propyl]-3-[2-(1H-indol-3-yl)-ethyl]-urea, which
  9. customwas separated
  10. custompurified by flash chromatography on silica gel (70 g)

Sources & evidence

ORD record
ord-afae71ea8b974aedb074c2ff2c73c425
Source dataset
uspto-grants-2008_03
Patent number
US07348354B2

Reaction notes

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